Key result
Electrotonic modulation of repolarization by the activation sequence is highly pronounced in small hearts with murine-like action potentials (rat slope -1.03) compared to larger hearts (pig slope -0.26).
p-value: p=<0.0001
Electrotonic modulation of repolarization by the activation sequence is pronounced in small hearts with murine-like action potentials, and is significantly influenced by tissue architecture and action potential morphology.
May limit extrapolation of rodent repolarization data to larger hearts; leaves open relevance to human electrophysiology.
Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of -1.03 ± 0.59 and -0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of repolarization.
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Walton et al. (2013) studied Ventricular repolarization heterogeneity (n=17). Activation sequence modulation (pacing) vs. Different pacing locations and species (rat vs. pig) was evaluated on Slope of linear correlation between activation time (AT) and action potential duration (APD) (p=<0.0001). Electrotonic modulation of repolarization by the activation sequence is highly pronounced in small hearts with murine-like action potentials (rat slope -1.03) compared to larger hearts (pig slope -0.26).
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